{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:23:34Z","timestamp":1791235414296,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,2,28]],"date-time":"2012-02-28T00:00:00Z","timestamp":1330387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH"},{"name":"Authority for Research and Development, Hebrew University of Jerusalem"},{"name":"Hadassah Medical Center Young Clinician Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE syndrome) is an autoinflammatory syndrome recently described in children. We undertook this study to investigate the clinical phenotype, genetic cause, and immune dysregulation in 9 CANDLE syndrome patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genomic DNA from all patients was screened for mutations in <jats:italic>PSMB8<\/jats:italic> (proteasome subunit \u03b2 type 8). Cytokine levels were measured in sera from 3 patients. Skin biopsy samples were evaluated by immunohistochemistry, and blood microarray profile and STAT\u20101 phosphorylation were assessed in 4 patients and 3 patients, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>One patient was homozygous for a novel nonsense mutation in <jats:italic>PSMB8<\/jats:italic> (c.405C&gt;A), suggesting a protein truncation; 4 patients were homozygous and 2 were heterozygous for a previously reported missense mutation (c.224C&gt;T); and 1 patient showed no mutation. None of these sequence changes was observed in chromosomes from 750 healthy controls. Of the 4 patients with the same mutation, only 2 shared the same haplotype, indicating a mutational hot spot. <jats:italic>PSMB8<\/jats:italic> mutation\u2013positive and \u2013negative patients expressed high levels of interferon\u2010\u03b3 (IFN\u03b3)\u2013inducible protein 10. Levels of monocyte chemotactic protein 1, interleukin\u20106 (IL\u20106), and IL\u20101 receptor antagonist were moderately elevated. Microarray profiles and monocyte STAT\u20101 activation suggested a unique IFN signaling signature, unlike in other autoinflammatory disorders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CANDLE syndrome is caused by mutations in <jats:italic>PSMB8<\/jats:italic>, a gene recently reported to cause \u201cJMP\u201d syndrome (joint contractures, muscle atrophy, microcytic anemia, and panniculitis\u2010induced childhood\u2010onset lipodystrophy) in adults. We extend the clinical and pathogenic description of this novel autoinflammatory syndrome, thereby expanding the clinical and genetic disease spectrum of <jats:italic>PSMB8<\/jats:italic>\u2010associated disorders. IFN may be a key mediator of the inflammatory response and may present a therapeutic target.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.33368","type":"journal-article","created":{"date-parts":[[2011,9,28]],"date-time":"2011-09-28T02:33:44Z","timestamp":1317177224000},"page":"895-907","source":"Crossref","is-referenced-by-count":379,"title":["Mutations in proteasome subunit \u03b2 type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity"],"prefix":"10.1002","volume":"64","author":[{"given":"Yin","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuval","family":"Ramot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Torrelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy 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